Morbidity of endomyocardial biopsy in cardiomyopathy.
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Arrhythmias, Cardiac↗
Biomedical subjects
D V Unverferth
Publications and source records attributed to D V Unverferth.
Serum and tissue magnesium concentrations in patients with heart failure and serious ventricular arrhythmias.
OBJECTIVE: To compare magnesium concentrations in serum and tissue from patients with heart failure. Two groups of patients were compared, those with or without serious ventricular arrhythmias. DESIGN: Consecutive enrollment. Blinded laboratory analyses. SETTING: Referral inpatient service of the cardiology division of a university hospital. PATIENTS: Twenty-three patients with idiopathic dilated cardiomyopathy and mild to moderately severe congestive heart failure (New York Heart Association functional class II to IV) were divided into two groups: 9 patients with sustained ventricular tachycardias and 14 patients without serious ventricular arrhythmias (control). INTERVENTIONS: Medications for heart failure were withdrawn 12 hours or more before study. Antiarrhythmic therapy was continued throughout the study. MEASUREMENTS AND MAIN RESULTS: The patients had skeletal muscle biopsies, myocardial biopsies, and blood sampling for the analysis of magnesium concentrations. No statistically significant differences in the mean magnesium concentrations in serum, circulating mononuclear cells, skeletal muscle, and myocardium were found when the 9 patients with ventricular arrhythmias were compared with the 14 control patients without serious ventricular arrhythmias. CONCLUSIONS: In a general, ambulatory sample of patients with heart failure, magnesium depletion in serum and tissue does not appear to occur more commonly in patients with serious ventricular arrhythmias than in patients without serious ventricular arrhythmias.
Adult↗
Cyclic adenosine monophosphate content of endomyocardial tissue obtained by biopsy in cyclosporine immunosuppressed human cardiac transplant recipients.
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Biopsy, Needle↗
Rest and exercise cardiovascular effects of terazosin in congestive heart failure.
This study investigated the acute effects of the alpha 1 antagonist terazosin on myocardial circulatory responses at rest and during exercise. Ten patients with congestive heart failure (class III and IV) underwent hemodynamic evaluation before and after a 5-mg oral dose of terazosin. At rest and during exercise, terazosin significantly decreased pulmonary capillary wedge pressure, systemic vascular resistance and mean arterial pressure while cardiac index increased. Stroke volume index increased (p less than 0.01) during exercise while left ventricular stroke work index remained unchanged in both experimental conditions. Terazosin administration significantly decreased both rest and exercise myocardial oxygen consumption while exercise coronary sinus oxygen content increased and arterial-coronary sinus oxygen difference diminished (p less than 0.05). Parallel with these changes, alpha blockade decreased the ratio of coronary blood flow to total cardiac output. Coronary vascular resistance remained unaltered with alpha blockade both at rest and during exercise. Coronary blood flow tended to diminish with decreased myocardial oxygen demand. Alpha 1 blockade induces systemic vasodilation and improves myocardial circulatory parameters without inducing coronary dilation or altering metabolic autoregulation.
Adrenergic alpha-Antagonists↗
Influence of positive inotropic therapy on pulsatile hydraulic load and ventricular-vascular coupling in congestive heart failure.
The aortic input impedance spectrum provides a description of the total hydraulic load imposed on the left ventricle and may be used to assess the coupling of the ventricle to the vasculature. The adaptation of the vasculature to positive inotropic intervention was examined in 10 patients with idiopathic dilated cardiomyopathy to test the hypothesis that increased myocardial contractility is matched by complementary changes in aortic impedance that optimize ventricular-vascular coupling and maximize power transfer to the circulation. High fidelity intravascular recordings of aortic pressure and flow were obtained at baseline study and during infusion of dobutamine to derive the aortic input impedance spectrum. In eight patients in whom increased staged infusion of dobutamine resulted in a significant increase in stroke volume (22.3 +/- 14.5 ml/beat increase over baseline), the significant (p less than 0.05) increase in the maximum of the first derivative left ventricular pressure pulse (dP/dt) was accompanied by significant decreases in characteristic impedance of the aorta (138 +/- 88 to 92 +/- 44 dyne.s.cm-5) wave reflection index (238 +/- 144 to 109 +/- 59 dyne.s.cm-5), and low frequency moduli of impedance. Effective positive inotropic therapy with dobutamine in the setting of congestive heart failure is accompanied by complementary changes in the aortic impedance spectrum, which represent a matching of impedance to the increased contractile state of the ventricle and facilitation of ventricular-vascular coupling.
Adult↗
Magnesium content of serum, circulating mononuclear cells, skeletal muscle, and myocardium in congestive heart failure.
Deranged magnesium concentrations in serum and cardiovascular structures have been implicated in the pathophysiology of hypertension, ischemic heart disease, arrhythmias, and sudden death. This study was conducted to determine the status and interrelation of serum and tissue concentrations of magnesium in patients with congestive heart failure, a clinical setting purportedly predisposed to the development of depleted levels of this cation. Magnesium concentrations of serum, circulating mononuclear cells, skeletal muscle, and myocardium were measured in 23 patients with heart failure on standard therapy. Two patients were hypomagnesemic (less than 1.6 meq/l). Poor or no correlations were found between serum and tissue magnesium concentrations and among the magnesium concentrations of the three tissues studied. Strong direct correlations were, however, noted between magnesium and potassium concentrations of the tissues examined. The prevalence of hypomagnesemia in this typical ambulatory heart failure population is relatively low (9%) and serum, circulating mononuclear cell, skeletal muscle, and myocardial magnesium concentrations correlate poorly with each other. Serum, circulating mononuclear cell, and skeletal muscle magnesium concentrations are thus of little predictive value in assessing the status of myocardial magnesium in humans with heart failure.
Adult↗
Successful management of acute myocarditis with biventricular assist devices and cardiac transplantation.
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Acute Disease↗
Cardiovascular pharmacology of dopexamine in low output congestive heart failure.
Dose-response infusions (0.25 to 4.0 micrograms/kg/min) and extended infusions of dopexamine, a new synthetic catechol with beta 2 adrenergic and dopaminergic agonist effects, were performed in 12 patients with low output congestive heart failure (CHF). The central and regional hemodynamic effects and responses in renal function were determined and compared with those of saline-placebo control patients in a randomized, double-blind, crossover design. Dopexamine significantly increased cardiac output at a dose greater than or equal to 0.25 micrograms/kg/min secondary to an increase in stroke volume at greater than or equal to 0.25 micrograms/kg/min and heart rate at greater than or equal to 0.50 micrograms/kg/min. Dopexamine evoked a significant decrease in systemic and pulmonary vascular resistances, with mild reductions noted for systemic and pulmonary diastolic pressures. Right and left ventricular filling pressures decreased over the entire dose range of dopexamine concomitant with a demonstrable improvement in the indexes of ventricular performance. Dopexamine preferentially increased visceral (renal, hepatic-splanchnic) blood flow over that of limb. Urine volume and sodium excretion increased slightly with dopexamine. Dopexamine elicits rather prominent vasodilating effects (particularly of visceral vascular beds), some positive inotropy and chronotropy and favorable responses in renal function.
Adrenergic Agonists↗
Pulsus alternans induced by inferior vena caval occlusion in man.
To assess the effect of rapid preload reduction on left ventricular performance in nonischemic cardiomyopathy, 11 patients were studied during inferior vena caval (IVC) balloon occlusion. Five developed sustained pulsus alternans. During pulsus alternans, the strong beats demonstrated systolic performance characteristics similar to baseline values, despite a drop in both left ventricular (LV) end-diastolic diameter (66 +/- 13 to 61 +/- 13 mm; p less than 0.05) and LV end-diastolic pressure (21 +/- 8 to 9 +/- 6 mmHg; p less than 0.05). In contrast, the weak beats demonstrated a reduction in peak systolic pressure (130 +/- 36 to 109 +/- 33 mmHg; p less than 0.02), fractional shortening (20% +/- 4% to 17% +/- 9%; p less than 0.05) and peak positive dP/dt (1,006 +/- 224 to 921 +/- 287 mmHg; p less than 0.05). Measures of diastolic performance (peak negative dP/dt, the time constant of LV relaxation, the length of diastasis, and LV end-diastolic stress) were not different between baseline beats and the strong beats; and only LV end-diastolic stress differed when baseline beats were compared to the weak beats. When the strong beats were compared to the weak beats during induced pulsus alternans, significant differences were observed in peak systolic pressure, peak positive dP/dt, and fractional shortening, but no differences in any measured diastolic parameter was observed. A slight difference was noted in the left ventricular end-diastolic diameters, with the weak beat consistently beginning at a slightly smaller diameter (61 +/- 13; mm vs 59 +/- 13; p less than 0.05). In summary, these data are consistent with an augmentation and deletion of intrinsic contractile forces in association with an alternation in preload on a beat-to-beat basis as best describing left ventricular performance during pulsus alternans.
Blood Pressure↗
Hemodynamic responses to different levels of alpha-adrenergic interruption in congestive heart failure.
The effects of prazosin, clonidine, and indoramin on central and regional hemodynamic parameters and left ventricular performance were analyzed in a congestive heart failure population to compare the pharmacodynamic responses to different levels of alpha-adrenergic interruption in this condition. The sympathetic nervous system is blocked at the peripheral alpha1-receptor by prazosin, at central nervous system alpha-receptor sites (via alpha-adrenoceptor agonism) by clonidine, and at peripheral and central sites by indoramin. Prazosin and indoramin produced reductions in total systemic and pulmonary vascular resistances, mean systemic and pulmonary artery pressures, and pulmonary capillary wedge pressure with little change in heart rate. Both agents selectively increased hepatic blood flow. Clonidine also decreased pulmonary artery pressure and vascular resistance, but evoked negative inotropic and chronotropic activity and did not alter regional blood flow. In contrast to prazosin, indoramin and clonidine did not augment cardiac output or stroke volume. In the setting of congestive heart failure, the central and regional hemodynamic effects and the responses in left ventricular performance vary considerably depending on the site of alpha-adrenergic interruption.
Adrenergic alpha-Antagonists↗
Preservation of the end-systolic pressure/end-systolic dimension relation following pindolol in congestive heart failure.
Beta blockade may adversely affect inotropic state of the ventricle, resulting in exacerbation of congestive heart failure in subjects with reduced ventricular function. In normal subjects, ventricular contractility appears to be preserved following administration of beta blockers with intrinsic sympathomimetic activity (ISA). The inotropic state of the ventricle was assessed in seven subjects with congestive heart failure (mean ejection fraction = 23 +/- 5%) before and after administration of the ISA beta blocker, pindolol, with the use of the noninvasively derived end-systolic pressure/end-systolic dimension (ESP/ESD) relation. The mean slope of the ESP/ESD relation was 36.3 +/- 20.4 mm Hg/cm at baseline and increased to 45.0 +/- 25.2 mm Hg/cm following five consecutive 10 mg oral doses of pindolol (p = ns). Other simultaneously derived inotropic indices that included percent fractional shortening, mean delta P/delta T, velocity of circumferential fiber shortening, and preejection period-to-left ventricular ejection time ratio showed directionally similar changes toward a mild increase in contractility. These results indicate that the slope of the left ventricular ESP/ESD relation is not altered following repeated dosing with pindolol in subjects with congestive heart failure. This reflects a preservation of inotropic state following administration of this ISA beta blocker in a population with severely compromised ventricular function.
Echocardiography↗
Central and regional hemodynamic effects of oral enoximone in congestive heart failure: a double-blind, placebo-controlled study.
Twelve patients with congestive heart failure underwent a double-blind, placebo-controlled study for the purpose of examining the central and regional hemodynamic effects of first-dose (1 and 2 mg/kg) oral enoximone, a new phosphodiesterase III inhibitor. Enoximone augmented cardiac output, generally through a positive chronotropic response. Indices of left ventricular contractility, specifically stroke volume, delta P/delta t, fractional shortening rate, and the duration of the preejection period, were only modestly enhanced by enoximone. At 2 mg/kg, systemic vascular resistance fell below baseline values without affecting systemic blood pressure; these parameters were not altered by the 1 mg/kg dose. Both pulmonary artery pressure and pulmonary vascular resistance dropped below baseline and below placebo control for the 2 mg/kg dose. Enoximone at 2 mg/kg lowered right and left heart filling pressures below baseline. Examination of regional hemodynamic responses to both doses demonstrated a reduction in limb vascular resistance and an increase in limb blood flow proportional to the concomitant increase in cardiac output. Renal and hepatic-splanchnic blood flow and vascular resistances were not altered by enoximone. First-dose oral enoximone (1 and 2 mg/kg) alters hemodynamics in heart failure by predominant vasodilatation, particularly of limb-musculoskeletal and pulmonary vascular beds, some positive chronotropism, and modest positive inotropism.
Adult↗
Late systolic indices of ventricular function: noninvasive derivation in congestive heart failure.
The slopes of end-systolic pressure/end-systolic dimension and volume relations have been found to be relatively load-independent indices of left ventricular contractility. Noninvasive determination of these relationships has been performed in normal subjects and has been found to reflect baseline and drug-induced changes in ventricular contractility. Three late systolic indices of ventricular contractility were noninvasively determined in subjects with chronic congestive heart failure to determine the feasibility of the method and to assess the linearity and slopes of the relationships in this population. All relations were linear with individual correlation coefficients ranging from 0.86 to 0.99. The mean +/- SD slope was 42.8 +/- 26.4 mm Hg/cm for the end-systolic pressure-dimension relation, 0.59 +/- .42 mm Hg/ml for the end-systolic pressure-volume relation, and 48.7 +/- 32.2 mm Hg/cm for the peak systolic pressure-end-systolic dimension relation. All slopes were markedly reduced compared to those reported in normal individuals. The relative degree of depression was greater for the pressure-volume slope than for the pressure-dimension slope, which is explained by the relationship between volume and dimension in dilated ventricles. These data indicate that measurement of late systolic indices of ventricular contractility by this noninvasive technique is feasible in subjects with congestive heart failure and yields reduced slopes consistent with the diminished contractile state of this population. Pressure-volume rather than pressure-dimension relations may more accurately reflect inotropic state in dilated ventricles.
Cardiomyopathy, Dilated↗
Human myocardial adenosine triphosphatase activities in health and heart failure.
This study was designed to determine: (1) the myocardial adenosine triphosphatase (ATPase) activities of normal humans and patients with dilated cardiomyopathy and (2) whether ATPase activity is related to age, cause and severity of heart failure, and digitalis therapy. Endomyocardial biopsies were performed in 32 subjects. Results from six were normal. Ventricular failure in the other 26 was idiopathic (n = 15), familial (n = 3), alcohol induced (n = 5), or related to doxorubicin therapy (n = 3). The biopsies were analyzed for total, mitochondrial, Na+-K+, Ca++, and Mg++ ATPase activities. Total and mitochondrial ATPase activities correlated with left ventricular ejection fraction (r = 0.65 and 0.67, respectively; both p = 0.0001). Residual Mg++ ATPase activity correlated weakly with ventricular function as measured by echocardiography (p = 0.05). Na+-K+ ATPase activity was depressed in patients receiving digitalis (p = 0.01). These results suggest that progressive ventricular dysfunction may be associated with a progressive loss of total ATPase, mitochondrial ATPase and, to a lesser extent, Mg++ ATPase activity. Although depressed mitochondrial ATPase activity is not likely to be the primary cause of ventricular dysfunction, it could perpetuate failure by leading to inadequate production of adenosine triphosphate. Further study of ATPase activities may provide additional insight into the pathogenesis of cardiac failure.
Adenosine Triphosphatases↗
Extraction and measurement of myocardial nucleotides, nucleosides, and purine bases by high-performance liquid chromatography.
Nucleotides, nucleosides, and purine bases were extracted from human endomyocardial biopsies, freeze-clamped rat hearts, and porcine coronary sinus plasma. Perchloric acid extracts were neutralized with Freon-trioctylamine and analyzed at 250 nm by reverse-phase ion-pairing high-performance liquid chromatography. To achieve the sensitivity necessary for analyzing small (1-3 mg wet wt) tissue samples, a small-bore, 2.1-mm-internal-diameter, C18, 5-micron reverse-phase column and a flow rate of 0.2 ml/min were used. All of the myocardial nucleotides and AMP degradation products were resolved in a total separation time of 27 min with 30 mM KH2PO4, 7.5 mM tetrabutylammonium phosphate buffers, and binary pH and acetonitrile gradients.
Animals↗
Neurohumoral profile in congestive heart failure: response to beta-blockade.
Beta-blockade has been reported to have beneficial hemodynamic effects in chronic congestive heart failure that may be related to alterations in the abnormal neurohumoral profile characteristic of this population. To determine the relationship of the neurohumoral profile to the hemodynamic response to beta-blockade in patients with chronic congestive heart failure, neurohumoral and hemodynamic variables were measured in 10 subjects having congestive cardiomyopathy at baseline and after administration of the beta-blocker pindolol. Baseline stroke index was noted to have an inverse curvilinear relation with plasma norepinephrine (r = -0.69) and renin (r = -0.71) concentration. Pulmonary vascular resistance demonstrated a direct logarithmic relation with plasma norepinephrine concentration (r = 0.68). Increases in norepinephrine, dopamine, and epinephrine concentrations after dosing were noted, with the most marked increase in norepinephrine concentration being coincident with a significant decline in stroke volume index. Two patients not tolerating beta-blockade were characterized by having baseline norepinephrine concentrations 3 SD higher than those of the remaining patients, more marked increases in epinephrine concentration after dosing, and the most profoundly decompensated heart failure at baseline, as defined by the relationship between neurohumoral and hemodynamic variables. These observations suggest that increases in catecholamines after dosing reflect a compensatory response to the adverse hemodynamic-inotropic effects of beta-blockade in congestive heart failure. The neurohumoral profile and the relationship of neuroendocrine to hemodynamic parameters may be useful in delineating patients at risk for adverse hemodynamic effects of beta-blockade.
Adrenergic beta-Antagonists↗
Medical therapy of end-stage congestive and ischemic cardiomyopathy.
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Angiotensin-Converting Enzyme Inhibitors↗
A preliminary report of the effects of orally administered enoximone on regional hemodynamics in congestive heart failure.
Twelve patients with moderately severe congestive heart failure underwent the simultaneous determination of central and regional hemodynamics after administration of placebo and enoximone. The regions examined hemodynamically included renal, hepatic-splanchnic and upper limb. Enoximone was studied in 2 doses, 1 and 2 mg/kg, and administered in a double-blind, placebo-controlled, crossover design. At these doses enoximone elicited a significantly greater increase in cardiac output and a greater decrease in systemic vascular resistance than placebo. Systemic blood pressure was not significantly altered. Enoximone did not significantly change the flow or resistance of renal or hepatic-splanchnic vascular beds. Limb vascular resistance decreased modestly after enoximone with a significant augmentation (+12% to 17%) of limb blood flow compared with placebo. The initial oral administration of the 1 and 2 mg/kg doses of enoximone improved central hemodynamic parameters with apparent preferential reduction of limb vascular resistance and augmentation of blood flow to the limb region (peripheral musculoskeletal system).
Administration, Oral↗